CZ20013691A3 - Process for preparing substituted pyrimidines - Google Patents

Abstract

The invention relates to a process for the preparation of substituted pyrimidines of formula (I), wherein R<1>, R<2>, R<3>, R<4> and X are as defined in Claim 1, which comprises reacting an amidine of formula (II), or a salt thereof, with a 3,3-disubstituted vinylcarbonyl compound of formula (III), wherein L represents a halogen atom or a group of formula -X-R<2>, (a) in an inert solvent, in the presence of a base and a compound of formula (IV): H-X-R<2>, in the event that L represents a halogen atom, or (b) in an inert solvent and in the presence of a base, in the event that L represents a group of formula -X-R<2>.

Description

A process for preparing a substituted pyrimidine derivative

Technical field

The invention relates to a process for the preparation of a substituted pyrimidine derivative.

BACKGROUND OF THE INVENTION

Pyrimidines which are substituted in the 4-position by hydrocarbyloxy or hydrocarbylthio are of great commercial importance as highly effective pesticidal or pharmaceutical compositions. U.S. Pat. No. 3,498,984 discloses 2-phenyl-4-thiopyrimidines having pharmaceutical properties. U.S. Pat. No. 5,824,624 discloses herbicidal compositions comprising 2-phenyl-4-oxypyrimidines. International Publication Nos. WO 98/40379 and WO 98/56789 disclose herbicidal 4-oxypyrimidines having a five-membered heteroaromatic group bonded at the 2-position of the pyrimidine moiety.

These compounds are prepared, for example, by a multi-step process involving treatment of benzimidine hydrochloride with substituted acetylacetate in the presence of a strong base to give 2-phenylpyrimid-4-one which is subsequently treated with a halogenating agent, especially phosphoryl halide to give 4-halo-2-phenylpyrimidine. alcohol or thioalcohol.

However, this method cannot be used to produce relatively large quantities on an industrial scale due to the risk of uncontrolled heat generation during the aqueous treatment in the halogenation stage.

W. Schroth et al. (Z. Chem. 24: 435-436 (1984))

discloses a process for the preparation of 1,3-thiazine-6-thions by condensation of 3,3-dichloroacrolein and thioamides in the presence of trifluoroborane. However, there is no suggestion in this disclosure to use such a reaction to prepare substituted pyrimidines, especially since trifluoroborane does not appear to be useful for large-scale production.

SUMMARY OF THE INVENTION

An efficient and efficient process for preparing a substituted pyrimidine derivative of the Formula I

where it means

R ¹ and R ² are independently an optionally substituted alkyl, cycloalkyl, phenyl or heteroaryl,

R ³ and R ⁴ are independently hydrogen or optionally substituted alkyl or phenyl,

The oxygen or sulfur atom X according to the invention consists in reacting the amidine of the formula II

R

NH ₂

C ¹ ) wherein R ¹ is as defined above, or a salt thereof at the 3,3-position with a disubstituted vinyl carbonyl compound of formula III

L '

L (III) where is

L is halogen or a group of formula -XR ²

R ^2, R ³ and R ⁴ are as defined above,

a) in an inert solvent in the presence of a base and a compound of formula IV

X - X - R ^{2 (} CIV) wherein X and R ² are as defined above when L is a halogen atom, or

b) in an inert solvent in the presence of a base when L is -XR ² , wherein R ² is as defined above.

Accordingly, the present invention provides an efficient new process for the preparation of substituted pyrimidines, as explained in more detail below.

When any group, referred to as optionally substituted, is meant the substituents of the group commonly used in the modification and / or development of pesticide or pharmaceutical compounds, and in particular substituents which maintain or promote herbicidal activity associated with the compounds of the invention or affect sustainability, soil penetration or in plants or any other desired property of such herbicidally active compounds. Each part of the molecule may contain one or more identical or different substituents.

With respect to the abovementioned moieties as optionally substituted alkyl or cycloalkyl, specific examples of such substituents include phenyl, halogen, nitro, cyano, hydroxyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy and alkoxycarbonyl C 1 -C 4 -alkyloxy group 1u4 «·

With respect to the abovementioned moieties as an optionally substituted phenyl or heteroaryl group, specific examples of such substituents are halogen atoms, in particular fluorine, chlorine and bromine, and nitro, cyano, amino, hydroxyl, alkyl of 1 to 4 carbon atoms, alkoxy C 1 -C 4 haloalkyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylthio, halogen sulfanyl groups such as SF 5. Suitably, 1 to 5 substituents may be used, with 1 to 2 substituents being preferred. Generally, haloalkyl, haloalkoxy and haloethio groups are trifluoromethyl, trifluoromethoxy, difluoromethoxy and trifluoromethylthio.

In general, and unless otherwise indicated, the term alkyl means a straight or branched chain group or moiety, generally having up to 10 carbon atoms, in particular up to 6 carbon atoms. Preferred are alkyl groups having 1 to 6 carbon atoms, in particular 1 to 3 carbon atoms. A preferred alkyl group is a methyl group and especially an ethyl group.

Generally and unless otherwise indicated, the term cycloalkyl means a group or moiety of up to 10 carbon atoms, in particular up to 8 carbon atoms. Preferred are cycloalkyl groups having 3 to 6 carbon atoms, especially 3 or 6 carbon atoms. A preferred cycloalkyl group is a cyclopropyl group, a cyclopentyl group and a cyclohexyl group.

In general and unless otherwise indicated, the term heteroaryl refers to a nitrogen containing five- or six-membered heteroaromatic group or moiety. Such a group generally has at least one nitrogen atom and, in the case of a five-membered ring, optionally one oxygen or sulfur atom. Such groups are preferably selected from the group consisting of a five-membered azole group; an azole, triazole, thiazole, isothiazole, thiadiazole, and in particular pyrrole and pyrazole and a 6-membered azine and diazine group, especially a pyridine, pyrimidine, pyridazine and pyrazine group.

Preferably R ¹ represents optionally substituted phenyl, pyrid-3-yl, pyridazin-2-yl, pyrazin-3-yl, thiazol-2-yl, oxazol-2-yl, 1,3,4-thiadiazol-2- ylove,

1,2,4-oxadiazol-2-yl, 1,3,4-oxadiazol-2-yl, pyrazol-1-yl or cycloalkyl of 3 to 6 carbon atoms.

Preferably R ² is optionally substituted phenyl- salicylic, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, pyrazol-5-yl, pyridazin-2-yl or cycloalkyl having 3 to 6 carbon atoms.

R ¹ and R ² independently of one another are preferably substituted by one or more alkyl, fluoroalkyl, alkoxy or fluoroalkoxy groups.

Suitable bases are weak organic or inorganic bases, preferably an alkali hydrogen carbonate such as sodium hydrogen carbonate, alkali carbonates such as potassium carbonate or sodium carbonate, and tertiary amines such as pyridine or triethylamine.

Further preferred embodiments of the methods of the invention include:

- the reaction is carried out in the presence of a base selected from the group consisting of alkali carbonates and tertiary amines, in particular potassium carbonate or sodium carbonate:

- the molar ratio of the amidine of formula II to the 3,3-disubstituted vinylcarbonyl compound of formula III is 1 = 5. · 1 · 1 up to 1: 0.5, especially 1: 1.5 · * · 1 1 1 1 1 1 1 1 1 1 1 1 1 1 up to 1 = 0.7 and especially 1 = 1.1 to 1 = 0.9;

the reaction step comprises stirring a mixture comprising a substantially amidine of formula II and a 3,3-disubstituted vinylcarbonyl compound of formula III, an inert diluent, a base and an optionally substituted alcohol, thioalcohol, phenol,

or thiophenol at a temperature of 0 to 150 ° C, preferably 60 to 145 ° C

C, and in particular 80 to 140 C, and in particular at the boiling point of the diluent;

the inert diluent is selected from the group consisting of acetonitrile, benzene, toluene, xylene, hexane, cyclohexane, dichloromethane, carbon tetrachloride, diethyl ether, diisopropyl ether, tert-butyl methyl ether, 2,2-dimethoxypropane, dimethoxyethane, diethoxyethane, tetrahydrofuran, tetrahydropyran, tetrahydropyran, dimethylsilyl, dimethyl dimethylsulfoxide and dioxane and mixtures thereof, especially toluene, dimethoxyethane and acetonitrile;

R ¹ represents a phenyl group substituted with at least one substituent selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl and haloalkoxy, in particular phenyl substituted with one or two chlorine or fluorine atoms, one or two C 1 -C 4 alkyl groups, alkoxy groups C 1 -C 4 fluoroalkyl, C 1 -C 4 fluoroalkyl or C 1 -C 4 fluoroalkoxy, most preferably R ¹ is 4-trifluoromethylphenyl, difluoromethoxypyrid-2-yl or 1-methyl-3-trifluoromethylpyrazol-5-yl; a y1 group;

R ¹ and R ² independently represent phenyl substituted by at least one halogen atom and / or at least one alkyl, alkoxy, halogenoalkoxy keel or haloalkoxy, X is hydrogen kysli-

wherein the reaction step is carried out in the presence of a phenol which is substituted by at least one halogen atom and / or by at least one alkyl, alkoxy, haloalkyl or haloalkoxy group, particularly in the presence of a phenol substituted by one or two chlorine or fluorine atoms, one or two alkyl (C 1 -C 4) groups, (C 1 -C 4) alkoxy, (C 1 -C 4) fluoroalkyl or (C 1 -C 4) fluoroalkoxy groups, most preferably in the presence of 3-trifluoromethylphenol:

and the 3,3-disubstituted vinylcarbonyl compound of formula III is 3,3-dichloroacrolein.

The compounds of the formula II or their salts are preferably substituted benzamidines or benzamidinium salts, in particular 4-trifluoromethylbenzamidine, which can be prepared from commercially available optionally substituted benzonitrile, in particular from 4-trifluoromethylbenzonitrile, by addition of ammonia or an ammonium salt.

Preferred benzamidinium salts are chlorides, sulfates, nitrates and carboxylates, especially acetates and thioglycolates.

The 3,3-disubstituted vinylcarbonyl compounds of formula III wherein L is halogen are commercially available or can be prepared by reacting tetrahalomethanes with vinyl ethers.

According to a preferred embodiment of the method according to the invention, it is

The 1,1,1,3-tetrahalogen-3-alkoxypropane obtained in this reaction can be hydrolyzed in situ to give the corresponding vinylcarbonyl compound of formula III which is subsequently reacted, preferably without prior isolation and / or purification steps, e.g. is in a single-pot method, with the compound of general formula II < 5 &gt;, &lt; 5 &gt; .

3,3-Disubstituted viny1karbonylove compound of formula III, wherein L represents a group of formula -XR ^2, wherein X and R ² has the above meanings, can be prepared by reacting a compound of formula III wherein L is halogen with a compound of formula IV

Η - R ² -X- IV) wherein X and R ² have the above meanings, optionally in the presence of a base.

The reaction of the amidine of the formula II, the 3,3-disubstituted vinylcarbonyl compound of the formula III and optionally the alcohol, phenol, thioalcohol or thiophenol is generally carried out at elevated temperature, preferably at a temperature of 35 to 150 ° C.

C, especially 80 to 145 C, and especially at the boiling point of the diluent.

The crude product obtained can be purified by methods known per se, for example by vacuum distillation, chromatographic methods or crystallization.

The reaction is generally complete in 5 to 50 hours, particularly in 10 to 25 hours.

In a particularly preferred embodiment of the invention 3,3-dichloroacrolein Cl mole) optionally diluted with an inert diluent, in particular acetonitrile three rim added to the mixture containing a benzamidine of formula II, wherein R ¹ represents optionally substituted phenyl, especially 4-Cl mole Trifluormethylbenzamidine , optionally substituted phenol, especially 3-trifluoromethylphenol (1.1 mol), potassium carbonate (3-5 mol) and diluent and the mixture is stirred at reflux. The reaction mixture is stirred for 10 to 40 hours at reflux temperature, then cooled to the solvent-phase and chromatography phase.

at room temperature and filtered. The organic fractions were removed in vacuo. The residue is washed with an organic solvent and distilled off. The residue is purified

Some of the compounds of formula (I) obtainable by the process of the invention are known, some are novel. Therefore, the invention also relates to novel compounds of formula IA

(CIA) wherein R ³ and R ⁴ are as defined in formula (I) and wherein is

R ^{1 is an} optionally substituted C 3 -C 8 cycloalkyl or pyrazin-2-yl group,

R ⁵ is a halogen atom or a haloalkyl group or a haloalkoxy group,

WV N-CH, S-CH, N-CH-CH, CH-CH-CH or N-NCR ⁶ ), where

R ^{6 is} C 1 -C 4 alkyl.

The invention is illustrated, but not limited, by the following examples.

Examples

Example 1

Process for preparing 4- (3-trifluoromethylphenoxy) -2- (4-trifluoromethylphenyl) pyrimidine

3,3-Dichloroacrolein (mmol10 mmol), diluted with acetonitrile (50 mL), is slowly added to a mixture containing 4-trifluoromethyl (10 · benzamidine ¢ 10 mmol), 3-trifluoromethylphenol (1 mmol), potassium carbonate ¢ 40 mmol) and acetonitrile 100 ml) and the mixture was stirred under reflux. When the addition of 3,3-dichloroacrolein is complete, additional 4-trifluoromethylbenzamidine (0.5 mmol) is added. The reaction mixture is stirred for 20 hours at reflux, then cooled to room temperature and filtered through silica. The organic phase was washed with ethyl acetate and concentrated in vacuo. The residue is purified by chromatography on alumina (petroleum ethers / ethyl acetate, 2/1) to give 3.25 g (85% of theory) of the pure product, m.p.

C.

Similarly prepare:

3-Methyl-4- (3-trifluoromethyl-phenoxy) -2- (4-trifluoromethyl-phenyl) -pyrimidine,

5-methyl-4- (3- (11-fluoromethylphenoxy) -2- (4 (4-fluoromethylphenyl) pyrimidine),

4-Phenoxy-2- (4-trifluoromethylphenyl) pyrimidine.

Examples 2 to 8

Process for the preparation of 4- (3- (trifluoromethylphenoxy) -2- (4-trifluoromethylphenyl) pyrimidine

Similar to Example 1, 4-trifluoromethylbenzamidine or a salt thereof is reacted with 3,3-dichloroacrolein in the presence of 3-trifluoromethylphenol in various solvents and at different temperatures.

The reagents and solvents, the reaction temperature and the yields are given in Table I, with the example number given in the first column and the following abbreviations being used:

TFBA 4-Trifluoromethylbenzamidine

TFBA. HCl 4-trifluoromethylbenzamidine hydrochloride

TFBA. Ac TFBA. TG TBME DME

4-Trifluoromethylbenzanediamine acetate 4-Trifluoromethylbenzamino-thioglycollate tert-butylmethyl ether dimethoxyethene

Table I

Default substance Dissolve the dough Temperature Yield (%) 2 TFBA acetonitri 1 reverse flow 85 3 TFBA DME reverse flow 85 4 TFBA toluene 90 ° C 72 5 TFBA TBME reverse flow 39 6 TFBA. HCl DME reverse flow 84 7 TFBA. Ac DME reverse flow 81 8 TFBA. TG DME reverse flow 47

Example 9

Process for preparing 4- (3-trifluoromethylphenoxy) -2- (4-trifluoromethylphenyl) pyrimidine

A mixture of 3,3-bis- (3-trifluoromethylphenoxy) acrolein (10 mmol), 4-trifluoromethylbenzamidine (10 mmol), potassium carbonate

(10 mmol) and acetonitrile (100 mL) were stirred at 80 ° C for four hours. The reaction mixture was then cooled to room temperature and filtered through silica. The organic phase was washed with ethyl acetate and concentrated in vacuo. The residue was purified by alumina chromatography (petroleum ethers / ethyl acetate, 2/1) to give 3.06 g (80% of theory) of pure product.

mp 66 C.

- 12.

• · ·

Example 10

Process for preparing 4- (3-trifluoromethylphenoxy) -2- (4-trifluoromethylphenyl) pyrimidine

3-Trifluoromethylphenol <5 mmol) was added followed by 3,3-dichloroacrolein <5 mmol) to the mixture containing 4-trifluoromethylbenzamidine sodium acetate. (5 mmol), potassium carbonate <40 mmol) and acetonitrile <35 mL). The reaction mixture was stirred for 20 hours under reflux. The reaction mixture was then cooled to room temperature and filtered through silica. The organic phase was washed with ethyl acetate and concentrated in vacuo. The residue is purified by chromatography on alumina (petroleum ethers / ethyl acetate, 2/1) to give 1.1 g (60%) of the pure product, m.p. 66-67 ° C.

Example 11

Simplified process for preparing 4- (3-trifluoromethylphenoxy) -2- (4-trifluoromethylphenyl) pyrimidine

Water (20 mmol) is added to a solution of 1,1,1,3-tetrachloro-3-ethoxypropane (10 mmol) in dimethoxyethane (25 mL). The reaction mixture was stirred at reflux for two hours. The resulting mixture was slowly added to a mixture containing 4-trifluoromethyl benzamidine hydrochloride (10 mmol), 3-trifluoromethylphenol (11 mmol), potassium carbonate (60 mmol) and dimethoxyethane (50 mL), which was stirred under reflux. When is adding

3,3-dichloro-acrolein is complete, additional 4-trifluoromethylbenzamidine hydrochloride <1 mmol) is added. The reaction mixture was stirred for 2 hours at reflux. The reaction mixture was then cooled to room temperature and filtered through silica. The organic phase was concentrated in vacuo. The residue is purified by chromatography on silica (petroleum ethers / diisopropyl ether, 6/1) to give 3.07 g (80% of theory) of the product.

- ..

mp 66-67 ° C;

Example 12

A process for the preparation of 2-C4-chlorophenyl) -4-C3-trifluoromethylphenoxy) pyrimidine

3,3-dichloroacrolein (10 mmol), diluted with dimethoxyethane (35 mL) was added slowly to a mixture containing 4-chlorobenzamidine hydrochloride (10 mmol), 3-trifluoromethylphenol (11 mmol), potassium carbonate (40 mmol) and dimethoxyethane (40 mL). The reaction mixture was stirred at reflux. When the addition of 3,3-dichloroacrolein is complete, additional 4-chlorobenzamidine hydrochloride (Cl mmol) is added. The reaction mixture was stirred for 3 hours at reflux. The reaction mixture was then allowed to cool to room temperature overnight and filtered through silica. The organic phase was concentrated in vacuo. The residue is purified by chromatography on alumina (ethyl ether / ethyl acetate, 20/1) to give 2.79 g (80% of theory) of the pure product, m.p.

Example 13

4-C3-Trifluoromethylphenoxy) -2-C4-fluorophenyl) pyrimidine

3,3-Dichloroacrolein (10 mmol), diluted with dimethoxyethane (35 ml), is slowly added to the mixture containing 4-fluorobenzamidine acetate. (10 mmol), 3-trifluoromethylphenol <11 mmol), potassium carbonate <40 mmol) and dimethoxyethane (40 mL). The reaction mixture was stirred at reflux. When the addition of 3,3-dichloroacrolein is complete, additional 4-fluorobenzamidine acetate (1 mmol) is added. The reaction mixture was stirred for 3 hours at reflux. The reaction mixture was then allowed to cool to room temperature overnight and filtered through silica. The organic phase was concentrated in vacuo. The residue was purified by alumina chromatography (petroleum ethers / ethyl acetate, 20/1) to give 2.52 g (75% of theory) of pure product, mp 52 C.

Example 14

A process for the preparation of 2-cyclopropyl-4- (3-trifluoromethylphenoxy) pyrimidine

Slowly add 3,3-dichloroacrolein (10 mmol), diluted with dimethoxyethane (35 mL), to a mixture containing cyclopropylcarbamidine hydrochloride (10 mmol), 3-trifluoromethylphenol (11 mmol), potassium carbonate (40 mmol) and dimethoxyethane (40 mL). The reaction mixture was stirred at reflux. When the addition of 3,3-dichloroacrolein is complete, additional cyclopropylcarbamidine hydrochloride (1 mmol) is added. The reaction mixture was stirred for 3 hours at reflux. The reaction mixture was then allowed to cool to room temperature overnight and filtered through silica. The organic phase was concentrated in vacuo. The residue was purified by alumina chromatography (petroleum ethers / ethyl acetate, 20/1) to give 2.1 g (75%) of pure product as a colorless liquid.

1 H NMR (CDCl ₃ , 5-2.10 ppm (m, N = C (= N) -CH)).

Example 15

2- (4-Fluorophenyl) -4- (5-trifluoromethyl-2-methylpyrazol-3-yloxy) pyrimidine

Water (20 mmol) was added to a solution of 1,1,1,3-tetrachloro-3-ethoxypropane (10 mmol) in dimethoxyethane (25 mL). Reaction o

the mixture was stirred for six and a half hours at 40 ° C. The resulting mixture was slowly added to a mixture containing 4-trifluorobenzamidine hydrochloride (10 mmol), 4-trifluoromethyl-2-methylpyrrole. Razol-1-one (11 mmol), potassium carbonate (60 mmol) and dimethoxyethane (50 mL), which is stirred under reflux. When the addition of 3,3-dichloroacrolein is complete, additional 4-trifluorobenzamidine hydrochloride (0.5 mmol) is added. The reaction mixture was stirred for 2 hours at reflux. The reaction mixture was then cooled to room temperature and filtered through silica. The organic phase was concentrated in vacuo. The residue is purified by chromatography on silica (petroleum ethers / ethyl acetate, 2/1) to give 1.40 g (46% of theory) of beige crystals, m.p. 101-102 ° C.

Example 16

Process for preparing 4- (2-difluoromethoxypyridin-4-yloxy) -2- (pyrazin-2-yl) pyrimidine

Water (20 mmol) was added to a solution of 1,1,1,3-tetrachloro-3-ethoxypropane (10 mmol) in dimethoxyethane (25 mL). Reaction o

The mixture was stirred for two hours at 60 ° C. The resulting mixture was slowly added to a mixture containing pyrazine-2-carboxamidine hydrochloride (10 mmol), 2-difluoromethoxypyridin-4-ol (10 mmol), potassium carbonate (60 mmol) and dimethoxyethane. (50 mL), which was stirred at reflux. When the addition of 3,3-dichloroacrolein is complete, additional pyrazine-2-carboxamidine hydrochloride (0.5 mmol) is added. The reaction mixture was stirred for 2 hours at reflux. The reaction mixture was then cooled to room temperature and filtered through silica. The organic phase was concentrated in vacuo. The residue is purified by chromatography on silica (ethyl acetate) to give 2.60 g (82% of theory) of beige crystals, m.p. 128-129 ° C.

Example 17

Process for preparing 4- (3-trifluoromethylphenoxy) -2- (3,5-dimethylpyrazol-1-yl) pyrimidine

Water (20 mmol) was added to a solution of 1,1,1,3-tetrachloro-3-ethoxypropane (10 mmol) in dimethoxyethane (25 mL). Reaction o

The mixture was stirred at 90 ° C for two hours. The resulting mixture was slowly added to a mixture containing 3,5-dimethylpyrazole-1-carboxamine (10 mmol). 3-trifluoromethylphenol (10 mmol), potassium carbonate (60 mmol) and dimethoxyethane (50 mL), which was stirred at reflux. When the addition of the 3,3-dichloroacrolein solution is complete, additional 3,5-dimethylpyrazole-1-carboxamidine nitrate (0.5 mmol) is added. The reaction mixture was stirred for 10 hours under reflux. The reaction mixture was then cooled to room temperature and filtered through silica. The organic phase was concentrated in vacuo. The residue was purified by chromatography on silica (ethyl acetate) to give 2.20 g of a yellow solid. The solid was washed with petroleum ether (50 mL) to give 1.75 g (52%) of colorless crystals, m.p. 101-102 ° C.

Industrial applicability

An efficient process for the production of substituted pyrimidines on an industrial scale by reacting an amidine with a 3,3-disubstituted vinylcarbonyl compound.

COMMON LAWYER OF ALL ZELtiM? KALENSKÝ ČVOPČÍK AND PARTNERS

120 00 Prague 2, Hálkova 2 Czech Republic

Claims (12)

PATENTOVÉ Claims A process for the preparation of a substituted pyrimidine derivative of the general formula I Cl) where is R ¹ and R ² are independently an optionally substituted alkyl, cycloalkyl, phenyl or heteroaryl, R ³ and R ⁴ are independently hydrogen or optionally substituted alkyl or phenyl, The oxygen or sulfur atom X according to the invention consists in reacting the amidine of the formula II Target) NH i '- / NH, wherein R ¹ is as defined above, or a salt thereof with 3,3-disubstituted viny1karbony1ovou compound of formula III Clil) Rs L Where is it L is halogen or a group of formula -XR ² R ^2, R ³ and R ⁴ are as defined above, 18 - ··· ······························································· a) in an inert solvent in the presence of a base and a compound of formula IV - X - R ² (IV) wherein X and R ² are as defined above when L is a halogen atom, or b) in an inert solvent in the presence of a base when L is -XR ² , wherein R ² is as defined above. Process according to claim 1, characterized in that the reaction is carried out in the presence of a base selected from the group consisting of alkali bicarbonates, alkali carbonates and tertiary amines. Process according to claim 1, characterized in that the reaction is carried out at a molar ratio of amidine of the formula II and 3,3-disubstituted vinyl 1 of the carbonyl compound of the formula III 1 = 5 to 1 = 0.5. A process according to claim 1, wherein the reaction step comprises mixing a mixture comprising a substantially amidine of formula II and a 3,3-disubstituted vinylcarbonyl compound of formula III, an inert diluent, a base and an optionally substituted alcohol, thioalcohol, phenol, or thiophenol at 0 to 150 C. 5. The process of claim 4 wherein the reaction is carried out in the presence of a diluent selected from acetonitrile, benzene, toluene, xylene, hexane, cyclohexane, dichloromethane, carbon tetrachloride, diethyl ether, diisopropyl ether, tert-butyl methyl ether, 2, 2, 2, 3, 2-dimethoxypropane, dimethoxyethane, diethoxyethane, tetrahydrofuran, tetrahydropyran, dimethylformamide, dimethylacetamide, n-methylpyrrolidone, dimethanol. • · 0 0 0 0 0 0 » And hylsulfoxide and dioxane and mixtures thereof. 6. The method according to claim 1, characterized. In that R ¹ is phenyl substituted with at least one halogen atom or at least one alkyl, alkoxy, haloalkyl or haloalkoxy. 7. The method according to claim 6, characterized in that R ¹ represents 4-trifluoromethylphenyl. A process according to claim 1 for the preparation of a 4-phenoxy-2-arylpyrimidine of formula I wherein R ¹ and R ^{2 are} each independently phenyl substituted with at least one halogen atom or at least one alkyl, alkoxy, haloalkyl or haloalkoxy group and X an oxygen atom, characterized in that the reaction step is carried out in the presence of a phenol substituted by at least one halogen atom and / or by at least one alkyl, alkoxy, haloalkyl or haloalkoxy group. The process according to claim 8, wherein the reaction step is carried out in the presence of 3-trifluoromethylphenyl. 10. The process of claim 1 wherein the 3,3-disubstituted vinylcarbonyl compound is 3,3-dichloroacrolein. 11. The process of claim 10 wherein the 3,3-dichloroacrolein is prepared in situ by hydrolysis of 1,1,1,3-tetrachloro-3-alkoxypropane. 12. Compound of Formula IA. • ♦ t 4 4 © © © © © © © © © © © © © © © © © © © © R ³ and R ⁴ are as defined in claim 1 and wherein is R ^{1 is an} optionally substituted C 3 -C 8 cycloalkyl or pyrazin-2-yl group, R ⁵ is a halogen atom or a haloalkyl group or a haloalkoxy group, W (N-CH, S-CH, N-CH-CH, CH-CH-CH or N-NCR ⁶ ). where it means R ^{6 is} C 1 -C 4 alkyl.